TASIGNA (nilotinib) is used to treat patients with a certain type of leukemia called Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML). Ph+ CML is a cancer of the blood that makes the body produce too many abnormal white blood cells. TASIGNA is used in adult patients with newly diagnosed Ph+ CML and in those with Ph+ CML in chronic or accelerated phase who are no longer benefiting from previous CML treatment, including treatment with Glivec^® (imatinib). TASIGNA is also used in adult Ph+ CML patients in chronic or accelerated phase who experienced side effects with previous CML treatment, including imatinib, and are not able to continue taking it.

TASIGNA powerfully and selectively inhibits BCR-ABL — an abnormal protein that is the key cause and driver of Ph+ CML — and stops the overproduction of abnormal white blood cells.

TASIGNA was designed to improve on imatinib by better inhibiting the BCR-ABL protein to block the signal that causes the body to produce too many damaged white blood cells. TASIGNA binds to this abnormal protein more tightly than does imatinib. Studies show that TASIGNA is more effective in newly diagnosed patients and also works for patients who are no longer benefiting from imatinib or who are unable to take imatinib due to side effects.

TASIGNA should not be used during pregnancy unless the clinical condition of the woman requires treatment with nilotinib. Patients who are pregnant or think that they may be pregnant should tell their doctor, who will discuss whether TASIGNA can be taken during the pregnancy.

Women who might get pregnant are advised to use effective contraception during treatment.

Breast-feeding is not recommended during treatment with TASIGNA. Patients should tell their doctor if they are breast-feeding.

TASIGNA contains lactose (milk sugar). If a patient has been told by the doctor that he or she has intolerance to some sugars, the patient should contact the doctor before taking this medicine.

Before taking TASIGNA, patients should tell their doctor if they:

• Have a heart disorder, such as an abnormal electrical signal called “prolongation of the QT interval”
• Are being treated with medicines that affect the heartbeat (antiarrhythmics) or the liver
• Suffer from lack of potassium or magnesium
• Have been treated with a medicine of the type called anthracyclines (frequently used in leukemia therapy)
• Have a liver or pancreas disorder

Patients should tell their doctor or pharmacist before taking TASIGNA if they are taking or have recently taken any other medicines, including over-the-counter medicines or herbal products. TASIGNA and certain other medicines can interact with each other. TASIGNA and other drugs are metabolized by enzymes in the liver. These enzymes may not work on several drugs at the same time. This can result in higher or lower than expected levels of TASIGNA or other drugs in the bloodstream. Some medications should be avoided during treatment with TASIGNA, including certain nonprescription medications and herbal products.

Examples of these drugs and supplements include, but are not limited to, the following:

• Antiarrhythmics — used to treat irregular heartbeat
• Chloroquine, halofantrine, clarithromycin, haloperidol, methadone, moxifloxacin — medicines that may have an unwanted effect on the function of the heart
• Ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin — used to treat infections
• Ritonavir — a medicine from the class “antiproteases” used to treat HIV
• Carbamazepine, phenobarbital, phenytoin — used to treat epilepsy
• Rifampicin — used to treat tuberculosis
• St. John’s wort — an herbal product used to treat depression and other conditions (also known as Hypericum perforatum)
• Midazolam — used to relieve anxiety before surgery
• Astemizole, terfenadine, cisapride, pimozide, quinidine, bepridil, or ergot alkaloids (ergotamine, dihydroergotamine)

If patients are taking any of these, their doctor might prescribe other alternative medicines. Patients should also tell their doctor if they are already taking TASIGNA and are prescribed a new medicine or wish to take an over-the-counter medicine or herbal product they have not taken previously during TASIGNA treatment.

TASIGNA needs to be taken on an empty stomach.

• Don’t take TASIGNA with grapefruit or other star fruit products because they may affect the levels of TASIGNA in the blood
• Take TASIGNA doses 12 hours apart
• This is important because food increases the blood level of TASIGNA in the body, which may lead to serious side effects
• Avoid eating any food for at least 2 hours before taking TASIGNA and at least 1 hour after taking TASIGNA

A simple rule can help patients remember how to take TASIGNA — 12-2-1!

12: Take TASIGNA doses 12 hours apart with a glass of water

2: Don’t eat or drink anything apart from water for at least 2 hours before taking TASIGNA

1: Don’t eat or drink anything apart from water for at least 1 hour after taking TASIGNA

Most side effects are mild to moderate and will generally disappear after a few days to a few weeks of treatment or can be managed with other medicines or treatments. However, in some cases, side effects can be serious or even life threatening. In these cases, TASIGNA therapy will likely be temporarily stopped and/or the dose lowered. However, in rare cases, TASIGNA therapy may be stopped permanently. The physician will monitor patients on a regular basis for signs or symptoms of serious side effects. The following information describes the most common side effects of TASIGNA:

• Low blood count
• Nausea, vomiting, or abdominal pain
• Swelling of hands, ankles, feet, or face
• Other common side effects include rash, headache, itching, tiredness, diarrhea, constipation, pain in joints or muscles

Also, patients should tell their doctor if they experience any of the following, as these may be signs of a more serious side effect:

• Irregularity in heart beat
• Unexplained bleeding or bruising
• Blood in urine or stool
• Shortness of breath
• Yellow skin and eyes (which may be signs of a liver disorder)
• Severe abdominal pain (which may be a sign of acute pancreatitis)
• Unexplained weakness

This is not a comprehensive list of all side effects recorded in clinical trials with TASIGNA. Patients should report any unusual symptoms to their health care provider.

Only the health care provider can tell whether TASIGNA is working. Patients will have regular tests, including blood tests, during treatment. These will monitor the levels of blood cells (white blood cells, red blood cells, and platelets) and the abnormal BCR-ABL protein in the body to see how TASIGNA is working. Physicians may also recommend periodic bone marrow samples.

Patients should continue taking TASIGNA every day for as long as their doctor tells them. This is intended to be a long-term treatment. Physicians will regularly monitor the patient's condition to check that the treatment is having the desired effect. If patients have questions about how long to take TASIGNA, they should talk to their doctor. Patients should not stop taking TASIGNA or change the amount of TASIGNA that they take unless their doctor tells them to. Patients with any further questions on the use of this product should ask their doctor or pharmacist.

If patients have taken more TASIGNA than they should have or if someone else accidentally takes their capsules, they should contact a doctor or hospital for advice immediately. The pack of capsules and the package leaflet should be shown to the doctor. Medical treatment may be necessary.

Patients who miss a dose should take the next dose as scheduled. Patients should not take a double dose to make up for the forgotten capsules.

TASIGNA should be kept out of the reach and sight of children. Do not use TASIGNA after the expiration date. The expiration date refers to the last day of that month. Do not store capsules above 30°C (86°F). Store in the original package in order to protect from moisture. Do not use any pack that is damaged or shows signs of tampering. Medicines should not be disposed of via wastewater or household waste.